A thorough understanding of the interrelationships of the extracellular matrix to its associated cells and to the endothelial and epithelial cells which circumscibe the matrix are becoming increasingly important in the maintenance of the septal wall of the distal lung and in the damage/repair of the matrix following deleterious perturbations. Although many factors modify lung structure and function, one of major clinical importance is the response of normal lung tissue to ionizing radiation. The two major radiation-induced responses are pneumonitis and fibrosis, both of which affect the morbidity and mortality of the host, and therefore make the lung the dose-limiting organ to clearly shown the type II pneumocyte, the source of pulmonary surfactant, to be an early target cell off radiation, providing a measurable dose-response increase in surfactant secretion. The type II cell response leads to both pneumonitis and fibrosis. Later studies have enabled us to bypass the pneumonitic stage without preventing fibrosis. Recent studies on the proteoglycan components of the extracellular matrix indicate that matrix alterations are 1) more sensitive than cellular, and 2) are detectable at lower exposures. Based on our extensive expertise in radiation toxicity of the lung, we propose to investigate the role of the extracellular matrix in the development and repair of lung injury, using radiation as the principle perturbation. These studies will be mounted via correlated multifaceted approaches, employing morphology (transmission electron microscopy, scanning electron microscopy, cytochemistry, immunocytochemistry, stereology, histology, autoradiography), laser flow cytometry and cell sorting (cell populations, cell cycle analysis, matrix-protein association) and biochemistry and tissue culture (cell adhesion, matrix affects on cell function, cell surface attachment sites). A clearer understanding of the structural-functional interrelationships of the extracellular matrix will enable us to generate regimens to prevent or retard lung injury, which would be of major clinical significance.